High resolution DNA detection methods and devices

Abstract

The present invention provides methods and devices for detecting a target nucleic acid molecule. A set of oligonucleotide probes integrated into an electric circuit, where the oligonucleotide probes are positioned such that they can not come into contact with one another, are contacted with a sample. If the sample contains a target nucleic acid molecule, one which has sequences complimentary to both probes, the target nucleic acid molecule can bridge the gap between the probes. The resulting bridge can then carry electrical current between the two probes, indicating the presence of the target nucleic acid molecule.

What is claimed:  
     
       1. A method for detecting a target nucleic acid molecule in a sample, said method comprising: 
       providing a device for detecting the presence of a target nucleic acid molecule in a sample, comprising:  
       two electrical conductors, including a first electrical conductor and a second electrical conductor, but where the electrical conductors are not in contact, and  
       one or more sets of two oligonucleotide probes attached to the electrical conductors, where the oligonucleotide probes are positioned such that the probes cannot come into contact with one another and such that a target nucleic acid molecule, which has two sequences, a first sequence complementary to a first probe attached to the first electrical conductor and a second sequence complementary to a second probe attached to the second electrical conductor, can be bound to both probes concurrently;  
       contacting the probes with a sample which may have the target nucleic acid molecule under selective hybridization conditions to permit target nucleic acid molecules, if any, present in the sample to hybridize to both of the probes;  
       filling the oligonucleotide probes and the selectively hybridized target nucleic acid molecule with a filling nucleic acid sequence, wherein the filling nucleic acid sequence is complementary to the target nucleic acid molecule and extends between the pair of oligonucleotide probes;  
       coating the oligonucleotide probes as well as any target nucleic acid molecule, and any filling nucleic acid sequence with a conductor; and  
       determining if an electrical current can be carried between the probes, said electrical current between the probes indicating the presence of the target nucleic acid molecule in the sample which has sequences complementary to the probes.  
     
     
       2. The method according to  claim 1 , wherein the nucleic acid molecule is DNA. 
     
     
       3. The method according to  claim 1 , wherein the nucleic acid molecule is RNA. 
     
     
       4. The method according to  claim 1 , wherein the conductor is silver. 
     
     
       5. The method according to  claim 1 , wherein the conductor is gold. 
     
     
       6. The method according to  claim 1  further comprising: 
       contacting the target nucleic acid molecule with nucleases after binding with the probes.  
     
     
       7. The method according to  claim 1  further comprising: 
       contacting the target nucleic acid molecule with ligase after binding with the probes and  
       heating the target nucleic acid molecule to a temperature high enough to denature a non-ligated target nucleic acid molecule from the probes.  
     
     
       8. The method according to  claim 1 , wherein the probes are complementary to sequences from the genetic material of a pathogenic bacteria. 
     
     
       9. The method according to  claim 8 , wherein the pathogenic bacteria is a biowarfare agent. 
     
     
       10. The method according to  claim 8 , wherein the pathogenic bacteria is a food borne pathogen. 
     
     
       11. The method according to  claim 1 , wherein the probes are complementary to sequences from the genetic material of a virus. 
     
     
       12. The method according to  claim 1 , wherein the probes are complementary to sequences from the genetic material of a human. 
     
     
       13. The method according to  claim 1 , wherein one or both of the probes has a sequence which is complementary to a sequence having a polymorphism, where the base or bases complementary to the polymorphism are located at an end of the probe distal to conductor.